Primary sclerosing cholangitis and recognitionof bile duct cancer: problem solved?

The risk of developing cholangiocarcinoma in the setting of primary sclerosing cholangitis (PSC) is in the range of 6-18 % [1] [2] [3] and is higher if a dominant stricture develops. In addition, approximately 10 % of PSC patients undergoing liver transplantation have undetected cholangiocarcinoma [4]. Screening is therefore of paramount importance, although the most effective screening strategy remains controversial.

Endoscopic retrograde cholangiography (ERC) is still considered to be the gold standard for diagnosing PSC, but it lacks sensitivity and specificity in differentiating between benign and malignant strictures [5]. Moreover, it is currently being strongly challenged by magnetic resonance cholangiopancreatography, even for initial diagnosis, since magnetic resonance imaging not only provides excellent images of the bile ducts but also additional information about the hepatic parenchyma [6]. The most widely used method of tissue sampling from a biliary stricture is brush cytology during ERC. The specificity of this technique reaches 100 % for malignancy, but with a sensitivity of only 60-70 %, which is insufficient for deciding the treatment plan [5] [7]. This highlights the need for additional methods of distinguishing between a malignant stricture and a benign one in this subgroup of patients.

Cholangioscopy has the advantage of direct visualization of the biliary tree and sampling of the biliary epithelium under direct visual control. Currently available cholangioscopes, with diameters ranging from 9 Fr to 10 Fr, can be passed through the working channel of a standard therapeutic duodenoscope, obviating the need for a cumbersome ”mother-daughter“ system or the percutaneous transhepatic approach that was previously used. In patients without PSC, several studies have reported that adding cholangioscopy to ERCP and tissue sampling improves the diagnostic ability and compensates for insufficient sensitivity [8] [9] [10]. In this issue of Endoscopy, Tischendorf et al. report their findings on the role of cholangioscopy in distinguishing between benign and malignant dominant strictures in patients with PSC [11]. In a well-conducted prospective study of 53 PSC patients with dominant strictures (12 of whom were eventually confirmed as having malignant strictures ), the authors showed that cholangioscopy was significantly superior to the ERCP findings for detecting malignancy with regard to sensitivity (92 % vs. 66 %; P = 0.25), specificity (93 % vs. 51 %, P < 0.001), accuracy (93 % vs. 55 %, P < 0.001), positive predictive value (79 % vs. 29 %, P < 0.001), and negative predictive value (97 % vs. 84 %, P < 0.001). Although one potential drawback of the study was that the comparison was made with standard ERC imaging without ductal brushing or biopsies, the reported sensitivity of cholangioscopy for detecting malignancy was higher than the previously reported sensitivity of brush cytology in PSC patients (92 % vs. 71 %) [5]. In all cases, even in the six patients with intrahepatic duct strictures, it was possible to pass the stricture with the 3-mm (9-Fr) cholangioscope after balloon dilation or bougienage, giving a technical success rate of 100 %. The cholangioscopic findings of malignant dominant strictures described included polypoid or villous masses and ulceratively destroyed mucosa. There was only one false-negative diagnosis of cholangioscopy, in a patient with erosive mucosal changes in the stenotic area who was initially classified as having a benign condition, although subsequent surgery revealed a well-differentiated cholangiocarcinoma. On the basis of these observations, the authors suggest that PSC patients with dominant bile duct strictures should undergo cholangioscopy, especially when the initial tissue sampling is benign.

Another recent publication studied the role of cholangioscopy in patients with PSC [12]. In this series of 41 patients, the indications for cholangioscopy were mixed, including evaluation of dominant strictures (n = 35) and stone removal (n = 6). The sensitivity and specificity of cholangioscopy for detecting malignant strictures was not calculated, as the study group included only a small number of PSC patients with a diagnosis of cholangiocarcinoma (n = 3). Nevertheless, the special aspect of this report was that cholangioscopy-guided biopsies from the biliary stricture were taken in 15 patients. This was done with a miniature biopsy forceps, which was passed through the 1.2-mm working channel of the 3.4-mm (10-Fr) cholangioscope. The adequacy of tissue sampling was satisfactory, with only one inadequate sample. In another recent study of patients with biliary strictures, conducted by the same group, cholangioscopy-guided biopsies correctly diagnosed malignancy in nine of 16 patients with confirmed malignant strictures [10].

Despite recent technical advances, cholangioscopy still has limitations. Access to small intrahepatic ducts is hampered by the relatively large caliber of current cholangioscopes and by the limitations of two-way tip deflection, which is smaller in video scopes (90° up and down) than in fiberoptic scopes (160° up and 130° down). All strictures require prior dilation before the cholangioscope is introduced, thus altering the appearance of the biliary epithelium and possibly leading to false-positive diagnoses of malignancy. In addition, the fragility of the scopes, the costs of repair, and the procedure time are currently factors that discourage more widespread use of cholangioscopy. Further developments such as four-way deflection, smaller diameters, and improvements in optical technology are likely to improve the diagnostic accuracy. The recent description of a four-way steerable catheter through which a fiberoptic probe as well as a miniature biopsy forceps can be passed may represent a major advance in this particular group of patients, as it has greater maneuverability, an increased tissue sampling capacity, and can be controlled by a single operator [13]. As Tischendorf et al. emphasize, PSC patients with a dominant stricture are certainly the group of patients in whom direct visualization (and directed biopsies) could be most beneficial.

Additional diagnostic modalities have yet to be explored in patients with PSC. Intraductal ultrasound has been shown to increase dramatically the detection rate of periductal masses in biliary strictures [14]. Optical coherence tomography is a novel high-resolution imaging technique that can depict biliary ductal epithelium and subepithelial structures [15]. Whether these techniques, in addition to their capabilities for detection, could help differentiate between benign and malignant strictures in PSC patients undoubtedly deserves further investigation.

References

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